In this application, Dr. Mescher proposes to continue his studies identifying ligands that are essential for the activation of naive and memory cytotoxic T lymphocytes. Utilizing both his pioneering system of artificial surfaces for the delivery of defined signals and an adoptive transfer of CTLs from transgenic TCR mice, Dr. Mescher proposes to confirm much of his preliminary work identifying the key signals responsible for triggering CTL activation. This renewal application is expanded to include experiments to define the potential role that IL-12 plays in activating the naive CTL response as well as investigating a potential role for inflammatory cytokines in influencing memory cell function. Two specific aims, which are essentially identical to the specific aims of the original project, with the important addition of the adoptive transgenic mouse system are proposed.